Thomas M. Van Vleet

Tonic and Phasic Alertness Training: A Novel Behavioral Therapy to Improve Spatial and Non-Spatial Attention in Patients with Hemispatial Neglect

Hemispatial neglect is a debilitating disorder marked by a constellation of spatial and non-spatial attention deficits. Patients’ alertness deficits have shown to interact with lateralized attention processes and correspondingly, improving tonic/general alertness as well as phasic/moment-to-moment alertness has shown to ameliorate spatial bias. However, improvements are often short-lived and inconsistent across tasks and patients. In an attempt to more effectively activate alertness mechanisms by exercising both tonic and phasic alertness, we employed a novel version of a continuous performance task (tonic and phasic alertness training, TAPAT). Using a between-subjects longitudinal design and employing sensitive outcome measures of spatial and non-spatial attention, we compared the effects of 9 days of TAPAT (36 min/day) in a group of patients with chronic neglect (N = 12) with a control group of chronic neglect patients (N = 12) who simply waited during the same training period. Compared to the control group, the group trained on TAPAT significantly improved on both spatial and non-spatial measures of attention with many patients failing to exhibit a lateralized attention bias at the end of training. TAPAT was effective for patients with a range of behavioral profiles and lesions, suggesting that its effectiveness may rely on distributed or lower-level attention mechanisms that are largely intact in patients with neglect. In a follow-up experiment, to determine if TAPAT is more effective in improving spatial attention than an active treatment that directly trains spatial attention, we trained three chronic neglect patients on both TAPAT and search training. In all three patients, TAPAT training was more effective in improving spatial attention than search training suggesting that, in chronic neglect, training alertness is a more effective treatment approach than directly training spatial attention.

Brain plasticity-based therapeutics

The primary objective of this review article is to summarize how the neuroscience of brain plasticity, exploiting new findings in fundamental, integrative and cognitive neuroscience, is changing the therapeutic landscape for professional communities addressing brain-based disorders and disease. After considering the neurological bases of training-driven neuroplasticity, we shall describe how this neuroscience-guided perspective distinguishes this new approach from (a) the more-behavioral, traditional clinical strategies of professional therapy practitioners, and (b) an even more widely applied pharmaceutical treatment model for neurological and psychiatric treatment domains. With that background, we shall argue that neuroplasticity-based treatments will be an important part of future best-treatment practices in neurological and psychiatric medicine.

Cross-training in hemispatial neglect: Auditory sustained attention training ameliorates visual attention deficits

Prominent deficits in spatial attention evident in patients with hemispatial neglect are often accompanied by equally prominent deficits in non-spatial attention (e.g., poor sustained and selective attention, pronounced vigilance decrement). A number of studies now show that deficits in non-spatial attention influence spatial attention. Treatment strategies focused on improving vigilance or sustained attention may effectively remediate neglect. For example, a recent study employing Tonic and Phasic Alertness Training (TAPAT), a task that requires monitoring a constant stream of hundreds of novel scenes, demonstrated group-level (n=12) improvements after training compared to a test-retest control group or active treatment control condition on measures of visual search, midpoint estimation and working memory (DeGutis and Van Vleet, 2010). To determine whether the modality of treatment or stimulus novelty are key factors to improving hemispatial neglect, we designed a similar continuous performance training task in which eight patients with chronic and moderate to severe neglect were challenged to rapidly and continuously discriminate a limited set of centrally presented auditory tones once a day for 9 days (36-min/day). All patients demonstrated significant improvement in several, untrained measures of spatial and non-spatial visual attention, and as a group failed to demonstrate a lateralized attention deficit 24-h post-training compared to a control group of chronic neglect patients who simply waited during the training period. The results indicate that TAPAT-related improvements in hemispatial neglect are likely due to improvements in the intrinsic regulation of supramodal, non-spatial attentional resources.

Modulation of non-spatial attention and the global/local processing bias.

Amelioration of the rightward spatial attention bias in patients with hemispatial neglect following manipulations of non-spatial attention suggests that spatial attention and mechanisms related to the regulation of attention are interrelated. Studies in normal, healthy subjects have shown similar modulation in spatial bias following tonic and phasic changes in attention suggesting that this interaction is a general mechanism of attention rather than a curiosity of the neglect disorder. The current study examined this attentional interaction to determine if perceptual processes favoring one hemisphere over the other are affected by this relationship. Participants first made rapid discriminations of Navon figures presented at central fixation. As expected, when participants attended to either the local or global dimension, incongruence in the orthogonal dimension resulted in longer reaction times for accurate discrimination compared to congruent trials. However, following a brief (16-min) continuous performance task designed to elicit behaviors associated with greater tonic and phasic alertness, participants showed significantly less local interference when attending the global dimension and more global interference when attending the local dimension on the Navon discrimination task compared to a control task condition. The results indicate that exercising tonic and phasic alertness produces a global processing bias.

Tonic and phasic alertness training: a novel treatment for executive control dysfunction following mild traumatic brain injury

Many individuals with traumatic brain injury (TBI) suffer difficulty regulating fundamental aspects of attention (focus, sustained attention) and may also exhibit hypo- or hyper-states of alertness. Deficits in the state of attention may underlie or exacerbate higher order executive dysfunction. Recent studies indicate that computerized cognitive training targeting attentional control and alertness can ameliorate attention deficits evident in patients with TBI or acquired brain injury. The current study examined whether improvements in attentional state following training can also influence performance on higher-order executive function and mood in individuals with mild TBI (mTBI). The current study examined five patients with executive control deficits as a result of mTBI, with or without persistent anxiety. Three patients engaged in ~5 hours of an executive control training task targeting inhibitory control and sustained attention; two additional patients were re-tested following the same period of time. Performance on standard neuropsychological measures of attention, executive function, and mood were evaluated pre- and post-training. The results indicate that tonic and phasic alertness training may improve higher-order executive function and mood regulation in individuals with TBI.

Implicit representation and explicit detection of features in patients with hemispatial neglect

Despite profound inattention to the side of space opposite a brain lesion in patients with unilateral neglect, priming studies demonstrate that undetected stimuli are capable of influencing subsequent behaviour. However, the nature of implicit processing of neglected stimuli is poorly understood. In the current study, we examined implicit processing in five patients with neglect using both visual search and priming methods. A psychophysical staircase method varying time of presentation was first used to establish a high (75%) and low (25%) detection probability for targets in both a feature and a conjunction search array. The arrays were then used in a priming task to examine how a difference in the level of overt detection of a feature or a conjunction presented in neglected space influenced subsequent discrimination speed to a single probe presented at fixation. The results showed that priming effects with feature primes were independent of their explicit detection rates (high versus low), but priming effects with conjunction primes reflected the pattern of explicit detection. These findings are discussed as they relate to availability versus accessibility of neglected stimuli.

Targeting alertness to improve cognition in older adults: A preliminary report of benefits in executive function and skill acquisition.

Efficient self-regulation of alertness declines with age exacerbating normal declines in performance across multiple cognitive domains, including learning and skill acquisition. Previous cognitive intervention studies have shown that it is possible to enhance alertness in patients with acquired brain injury and marked attention impairments, and that this benefit generalizes to improvements in more global cognitive functions. In the current preliminary studies, we sought to test whether this approach, that targets both tonic (over a period of minutes) and phasic (moment-to-moment) alertness, can improve key executive functioning declines in older adults, and enhance the rate of skill acquisition. The results of both Experiments 1 and 2 demonstrate that, compared to active control (AC) training, alertness training significantly enhanced performance in several validated executive function measures. In Experiment 2, alertness training significantly improved skill acquisition compared to AC training in a well-characterized speed of processing (SOP) task, with the largest benefits shown in the most challenging SOP blocks. The results of the current study suggest that targeting intrinsic alertness through cognitive training provides a novel approach to improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments.

The nonspatial side of spatial neglect and related approaches to treatment.

In addition to deficits in spatial attention, individuals with persistent spatial neglect almost universally exhibit nonspatially lateralized deficits in sustained and selective attention, and working memory. However, nonspatially lateralized deficits in neglect have received considerably less attention in the literature than deficits in spatial attention. This is in spite of the fact that nonspatially lateralized deficits better predict the chronicity and functional disability associated with neglect than spatially lateralized deficits. Furthermore, only a few treatment studies have specifically targeted nonspatially lateralized deficits as a means to improve spatial neglect. In this chapter, we will briefly review several models of spatial attention bias in neglect before focusing on nonspatial deficits and the mechanisms of nonspatial-spatial interactions and implications for treatment. Treatment approaches that more completely address nonspatial deficits and better account for their interactions with spatial attention will likely produce better outcomes.

Randomized control trial of computer-based rehabilitation of spatial neglect syndrome: the RESPONSE trial protocol

BackgroundSpatial neglect is a frequent and debilitating consequence of acquired brain injury and currently has no widely accepted standard of care. While previous interventions for spatial neglect have targeted patients’ overt spatial deficits (e.g., reduced contralesional visual scanning), far fewer have directly targeted patients’ non-spatial deficits (e.g., sustained attention deficits). Considering that non-spatial deficits have shown to be highly predictive of long-term disability, we developed a novel computer based training program that targets both sustained (tonic) and moment-to-moment (phasic) aspects of non-spatial attention (Tonic and Phasic Alertness Training, TAPAT). Preliminary studies demonstrate that TAPAT is safe and effective in improving both spatial and non-spatial attention deficits in the post-acute recovery phase in neglect patients. The purpose of the current trial (referred to as the REmediation of SPatial Neglect or RESPONSE trial) is to compare TAPAT to an active control training condition, include a larger sample of patients, and assess both cognitive and functional outcomes.Methods/DesignWe will employ a multi-site, longitudinal, blinded randomized controlled trial (RCT) design with a target sample of 114 patients with spatial neglect. Patients will either perform, at their home, the experimental TAPAT training program or an active control computer games condition for thirty minutes/day, five days a week, over three months. Patients will be assessed on a battery of cognitive and functional outcomes on three occasions: a) immediately before training, b) within forty-eight hours post completion of total training, and c) after a three-month no-contact period post completion of total training, to assess the longevity of potential training effects.DiscussionThe strengths of this protocol are that it tests an innovative, in-home administered treatment that targets a fundamental deficit in neglect, employs highly sensitive computer-based assessments of cognition as well as functional outcomes, and incorporates a large sample size (relative to other neglect treatment studies) in an RCT design.Trial registrationClinicalTrials.gov identifier, NCT01965951

Shifting attention in viewer- and object-based reference frames after unilateral brain injury

The aims of the present study were to investigate the respective roles that object- and viewer-based reference frames play in reorienting visual attention, and to assess their influence after unilateral brain injury. To do so, we studied 16 right hemisphere injured (RHI) and 13 left hemisphere injured (LHI) patients. We used a cueing design that manipulates the location of cues and targets relative to a display comprised of two rectangles (i.e., objects). Unlike previous studies with patients, we presented all cues at midline rather than in the left or right visual fields. Thus, in the critical conditions in which targets were presented laterally, reorienting of attention was always from a midline cue. Performance was measured for lateralized target detection as a function of viewer-based (contra- and ipsilesional sides) and object-based (requiring reorienting within or between objects) reference frames. As expected, contralesional detection was slower than ipsilesional detection for the patients. More importantly, objects influenced target detection differently in the contralesional and ipsilesional fields. Contralesionally, reorienting to a target within the cued object took longer than reorienting to a target in the same location but in the uncued object. This finding is consistent with object-based neglect. Ipsilesionally, the means were in the opposite direction. Furthermore, no significant difference was found in object-based influences between the patient groups (RHI vs. LHI). These findings are discussed in the context of reference frames used in reorienting attention for target detection.